RecruitingEarly Phase 1NCT06252402

CMV-specific HIV-CAR T Cells as Immunotherapy for HIV/AIDS

A Pilot Study to Evaluate the Feasibility and Safety of Cytomegalovirus-Specific, Anti-HIV Chimeric Antigen Receptor (CMV-HIV CAR) T Cells in People Living With HIV

Sponsor

City of Hope Medical Center

Enrollment

15 participants

Start Date

Dec 19, 2024

Study Type

INTERVENTIONAL

Conditions

HIV-1

Summary

Human immunodeficiency virus type 1 (HIV-1) causes a persistent infection that ultimately leads to acquired immunodeficiency syndrome (AIDS). Treatment of HIV-1 infection with combination anti-retroviral therapy (ART) suppresses HIV-1 replication to undetectable viral levels and saves lives. Nevertheless, ART cannot eradicate latent cellular reservoirs of the virus, and HIV-1 infection remains a life-long battle. Adoptive cellular immunotherapy using chimeric antigen receptor (CAR) engineered T cells directed against HIV-1 envelope subunit protein gp120 (HIVCAR T cells) may provide a safe and effective way to eliminate HIV-infected cells. However, the number of HIV-infected cells is low in participants under ART, and CAR T cells disappear if they are not stimulated by their target antigens. Interestingly, about 95% of HIV-1-infected individuals are CMV-seropositive and CMV-specific T cells have been shown to persist. To overcome the CAR T cells low persistence issue, we propose to make HIV-CAR T cells using autologous cytomegalovirus (CMV)-specific T cells, which can be stimulated by endogenous CMV in vivo. The overall hypothesis of this first-in-human Phase 1, open-label, single-arm study is that endogenous immune signals to CMV-specific T cells can maintain the presence of autologous bispecific CMV/HIV-CAR T cells in healthy people living with HIV-1 (PLWH), and achieve long-term remission in the presence of ART.

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This trial is testing a new type of cell therapy for people living with HIV. Scientists take the patient's own immune cells (T-cells), genetically engineer them to target HIV, and infuse them back into the body. The goal is to create a longer-lasting immune defense against HIV without relying solely on daily medication. **You may be eligible if...** - You are 18 or older with a documented HIV-1 infection - You have been on stable HIV medication (ART) for at least 48 weeks and your virus is undetectable - Your immune cell count (CD4+) is at least 450 cells/μL - You are generally in good health and willing to briefly pause your HIV medication before a blood collection procedure **You may NOT be eligible if...** - You have a serious other illness or complication - Your HIV has become resistant to two or more classes of antiviral drugs - You have previously received an experimental HIV therapy or gene therapy - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BIOLOGICALCMV/HIV-CAR T Cells

Eligible participants will temporarily interrupt their ART regimen for 4 days prior to leukapheresis to prevent residual cell drug levels that could inhibit lentiviral transduction of the T cells during CAR T cewll manufacturing. Participants will resume their ART regimen immediately after leukapheresis. Once the final cell product is released, participants will receive a single intravenous (IV)infusion of autologous CMV/HIV-CAT T cells (defined as Day 0). Up to three doses of CMV/HIV-CAR T cewlls may be explored.